The Pharmacogenomics of Selective Serotonin Reuptake Inhibitors

García-Marín, Luis M.; Rabinowitz, Jill A.; Ceja, Zuriel; Alcauter, Sarael; Medina-Rivera, Alejandra; Rentería, Miguel E.

doi:10.2217/pgs-2022-0037

Cited by 8 publications

(4 citation statements)

References 72 publications

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“…The most important issue is the low predictability of a single genetic variation to pharmacokinetics, efficacy, and safety of the drugs, and polygenic score analysis using several involved genetic variations has been increasingly attempted and reported. [21][22][23] For this purpose, a streamlined genotyping system, which can analyze several related variants simultaneously, is strongly desired.…”

Section: Discussionmentioning

confidence: 99%

Development of Novel Mass Spectrum-Based Assay for Simultaneous Detection of 36 Variants in the 14 Pharmacogenetic Genes for the Japanese Population

Yamamoto

Tanno

Tanaka³

et al. 2023

Biological & Pharmaceutical Bulletin

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Pharmacogenetics (PGx) enhances personalized care, often reducing medical costs, and improving patients' QOL. Unlike single variant analysis, multiplex PGx panel tests can result in applying comprehensive PGx-guided medication to maximize drug efficacy and minimize adverse reactions. Among PGx genes, drug-metabolizing enzymes and drug transporters have significant roles in the efficacy and safety of various pharmacotherapies. In this study, a genotyping panel has been developed for the Japanese population called PGx_JPN panel comprising 36 variants in 14 genes for drug-metabolizing enzymes and drug transporters using a mass spectrometry-based genotyping method, in which all the variants could be analyzed in two wells for multiplex analysis. The verification test exhibited good concordance with the results analyzed using the other standard genotyping methods (microarray, TaqMan assay, or another mass spectrometry-based commercial kit). However, copy number variations such as CYP2D6*5 could not apply to this system. In this study, we demonstrated that the mass spectrometry-based multiplex method could be useful for in the simultaneous genotyping of more than 30 variants, which are essential among the Japanese population in two wells, except for copy number variations. Further study is needed to assess our panel to demonstrate the clinical use of pharmacogenomics for precision medicine in the Japanese population.

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Section: Discussionmentioning

confidence: 99%

Development of Novel Mass Spectrum-Based Assay for Simultaneous Detection of 36 Variants in the 14 Pharmacogenetic Genes for the Japanese Population

Yamamoto

Tanno

Tanaka³

et al. 2023

Biological & Pharmaceutical Bulletin

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“…Consistently, previous studies have linked lithium 37 , nicotine 38 , and alcohol consumption 39 with an increased risk of developing cataracts. Citalopram, an antidepressant known as a selective serotonin reuptake inhibitor 40 , has been associated with an increased risk of cataract surgery 41 . The interaction between METTL21A and CREB1 with citalopram could be highlighting a mechanism that is triggered by citalopram and leads to an increased risk of cataracts.…”

Section: Discussionmentioning

confidence: 99%

Uncovering Novel Genetic Loci and Biological Pathways Associated with Age-Related Cataracts through GWAS Meta-Analysis

Díaz-Torres

Lee

García-Marín

et al. 2023

Preprint

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Background Age-related cataract is a highly prevalent eye disorder that results in the clouding of the crystalline lens and is one of the leading causes of visual impairment and blindness. The disease is influenced by multiple factors including genetics, prolonged exposure to ultraviolet radiation (UVR), and a history of diabetes. However, the extent to which each of these factors contributes to the development of cataracts remains unclear. Further research into the genetic basis of cataracts could provide valuable insights into the disease's etiology and lead to a better understanding of biological mechanisms that are associated with its development. Methods This study presents the largest genome-wide association study of cataracts to date, using data from 127,985 cases and 837,371 controls. We performed gene enrichment analysis to identify genes and biological pathways associated with cataracts. We integrated our results with gene expression reference datasets to identify genetic variants modifying risk for cataracts through changes in the expression of specific genes. We further explored drug-gene interactions to better understand the potential impact of pharmacological interventions on cataract development. Finally, we explored whether a causal relationship underlies the known comorbidity between type 1 diabetes and cataracts using a mendelian randomization framework, and the association between UV exposure and cataract risk in adults using a polygenic risk scoring approach. Findings Our study identified 85 independent genome-wide significant loci, 37 of which are novel. Gene-based association tests identified 126 genes associated with cataracts, hinting at a potential relationship between negative regulation of lipid biosynthesis and the development of cataracts. Four of the genes identified GNL3, JAG1, METTL21A, and CREB1 are involved in drug-gene interactions. Moreover, Mendelian Randomisation analysis identified a putative causal relationship between genetic predisposition to type 1 diabetes and an increased risk of cataracts. Lastly, we found evidence indicating that early-life exposure to UVR may have an impact on the later development of cataracts. Interpretation Our findings advance our understanding of the genetic basis of cataract and provide new insights into its etiology. We identified multiple genes and biological pathways associated with the condition, including associations with four genes from which drug repurposing could be proposed. Our results suggest a causal association between type 1 diabetes and cataracts. Also, we highlighted a surrogate measure of UV light exposure as a marker of cataract risk in adults and drug-genes interactions that has the potential of informing novel therapies.

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“…Depression is a common CNS disorder that can be treated with conventional antidepressants developed according to the monoamine dysfunction hypothesis, such as the selective serotonin reuptake inhibitors (García-Marín et al, 2022). However, these drugs exhibit a number of problems, such as low response rate (Kruizinga et al, 2021), the occurrence of sexual dysfunction (Bakr et al, 2022), and increasing suicide rates (Braun et al, 2016).…”

Section: Pharmacological Effects Of Sinomenine In Depressionmentioning

confidence: 99%

“…It is known that the development of depression is related to a variety of mechanisms, such as neuroinflammation (Yirmiya et al, 2015), brain-derived neurotrophic factor (BDNF) Frontiers in Pharmacology frontiersin.org dysfunction (Poon et al, 2021), and monoamine dysfunction (García-Marín et al, 2022). Inhibition of neuroinflammation may mediate the antidepressant effect of sinomenine, because administration of sinomenine (30, 100, or 300 mg/kg; oral administration, 21 days) can suppress the CUS-induced expression of IL-1β, IL-6, TNF-α, and NLRP3-inflammasome complexes such as NLRP3, ASC, and caspase-1 in the hippocampus of mice, probably by inhibiting p38 and NF-κB (Figure 6; Table 2) (Liu et al, 2018).…”

Section: Pharmacological Effects Of Sinomenine In Depressionmentioning

confidence: 99%

Potential therapeutic effects and pharmacological evidence of sinomenine in central nervous system disorders

Hong

et al. 2022

Front. Pharmacol.

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Sinomenine is a natural compound extracted from the medicinal plant Sinomenium acutum. Its supplementation has been shown to present benefits in a variety of animal models of central nervous system (CNS) disorders, such as cerebral ischemia, intracerebral hemorrhage, traumatic brain injury (TBI), Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, depression, multiple sclerosis, morphine tolerance, and glioma. Therefore, sinomenine is now considered a potential agent for the prevention and/or treatment of CNS disorders. Mechanistic studies have shown that inhibition of oxidative stress, microglia-or astrocyte-mediated neuroinflammation, and neuronal apoptosis are common mechanisms for the neuroprotective effects of sinomenine. Other mechanisms, including activation of nuclear factor E2-related factor 2 (Nrf2), induction of autophagy in response to inhibition of protein kinase B (Akt)-mammalian target of rapamycin (mTOR), and activation of cyclic adenosine monophosphate-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF), may also mediate the anti-glioma and neuroprotective effects of sinomenine. Sinomenine treatment has also been shown to enhance dopamine receptor D2 (DRD2)mediated nuclear translocation of αB-crystallin (CRYAB) in astrocytes, thereby suppressing neuroinflammation via inhibition of Signal Transducer and Activator of Transcription 3 (STAT3). In addition, sinomenine supplementation can suppress N-methyl-D-aspartate (NMDA) receptormediated Ca 2+ influx and induce γ-aminobutyric acid type A (GABA A ) receptor-mediated Cl − influx, each of which contributes to the improvement of morphine dependence and sleep disturbance. In this review, we outline the pharmacological effects and possible mechanisms of sinomenine in CNS disorders to advance the development of sinomenine as a new drug for the treatment of CNS disorders.

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The Pharmacogenomics of Selective Serotonin Reuptake Inhibitors

Cited by 8 publications

References 72 publications

Development of Novel Mass Spectrum-Based Assay for Simultaneous Detection of 36 Variants in the 14 Pharmacogenetic Genes for the Japanese Population

Development of Novel Mass Spectrum-Based Assay for Simultaneous Detection of 36 Variants in the 14 Pharmacogenetic Genes for the Japanese Population

Uncovering Novel Genetic Loci and Biological Pathways Associated with Age-Related Cataracts through GWAS Meta-Analysis

Potential therapeutic effects and pharmacological evidence of sinomenine in central nervous system disorders

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